The function of proteins is dependent on their subcellular localization. Since the original discovery that proteins are “tagged” by signal sequences recognized by specific receptors that determine their localization, research efforts are relentlessly seeking to understand how these receptors work. Nuclear transport receptors, collectively called karyopherins, represent a large family, which include importins and exportins, of crucial importance in transporting proteins either to the nucleus or to the cytoplasm across the nuclear envelope in concert with the small GTPase RAN.
In addition to this well-established function, work from our and other laboratories has shown that nuclear transport receptors take on new roles when cells enter mitosis and the nuclear envelope dissolves. Indeed: 1) classical experiments and “omics” approaches indicate that importin beta, the major nuclear import receptor, acts as a “master” regulator during mitosis and orchestrates the concerted localization of key factors at the mitotic apparatus and in chromosome segregation. 2) Importin beta is often deregulated in cancer and can be regarded as a proto-oncogene; this deregulated expression contributes to the genetic instability typical of cancer cells. 3) On the other hand, however, importin beta also modulates the sensitivity of cancer cells to therapeutic anti-mitotic drugs and thus represents a “vulnerability” that can be targeted in cancer. 4) Finally, an unexpected turn in importin function has emerged, with the recent rediscovery of an old inhibitor of parasitic infections, Invermectin, has proven capable to inhibit the replication of the sars-cov2 virus and has turned to act primarily as an inhibitor of importin beta. These data illustrate the multifaceted roles of nuclear transport receptors in cell life and duplication, with a wide reach in physiological processes and in diseases.
24 Aprile, ore 12, online
Prof. Patrizia Lavia
Istituto di Biologia e Patologia Molecolari (IBPM) CNR
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